Saturday, June 4, 2011

Blood Simple : Part 1: Sex Hormones by Jerry Brainum

Most of us involved in weight training are on a lifelong quest to maximize physical development and health. My quest has evolved over the years, and recently it’s taken a new turn: I’ve become aware of the major role that self-prescribed blood tests can play. If you’re not having regular blood tests and charting the results, you’re shortchanging yourself.

I’m a firm believer in blood testing as a diagnostic tool for bodybuilding as well as an early-warning system. The tests covered in the first installment of this series are the most bodybuilding-specific tests available, including those for testosterone, DHT and estrogen. If you’re not making the progress you think you should be making, your levels of those hormones may be the culprits. It makes no sense to train for hundreds of hours per year and spend thousands of dollars on supplements and gym memberships and not have this basic information. Invest in blood tests regularly, and you’ll know for sure. If you’ve ever used anabolic steroids, it’s even more important to get tested regularly.

There are two ways to have the tests performed. If your internist understands athletes, get what you can through your health insurance. You can also use independent labs that do this kind of testing confidentially. If you choose that route, you can be confident that you alone will get the results.
The bottom line is that you must be proactive about this. If you’re serious about bodybuilding, you need to know your numbers on these tests.                                                                                            
 —John Balik
 Steve was clearly agitated. He’d phoned me after receiving a call from his doctor’s office. Lab tests had showed that one of his liver enzymes was slightly elevated. The doctor ominously suggested that Steve undergo a series of liver-function tests to deduce the exact cause of the abnormal enzyme finding. But it turned out that this particular liver enzyme also exists in heart and muscle and that its blood levels rise when muscle is damaged. Unless you look at the levels of other liver enzymes, you can be led astray, as occurred in this case. Since Steve was a hard-training bodybuilder, minor elevation of one or two liver enzymes was normal.

Several years ago a famous and successful professional bodybuilder asked me to look at his lab results. Basically they revealed a man in exceptional health, but one test result caught my eye. His level of high-density lipoprotein (HDL), a protective form of cholesterol carrier in the blood, was listed as five. Normal levels start at 35, and the higher the figure, the better. Since low HDL levels are linked to cardiovascular disease, you might have concluded that Mr. Universe was in reality Mr. Dead Man Walking—unless you looked at his other blood lipid levels. His total cholesterol was only 120, making his HDL irrelevant. Besides, his blood had been tested while he was on an anabolic-steroid cycle, and some 17-alpha ankylated oral anabolic steroids speed HDL catabolism in the liver. Interestingly, although oral steroids are thought to increase the levels of certain liver enzymes, this man had no such symptoms.

Another bodybuilder panicked when told he might be facing incipient kidney failure, based on the “abnormal” findings of his urinalysis; his creatinine was about twice the normal level. But he’d failed to disclose that he’d been on a creatine-loading regime. After two days of taking creatine, the body passes more than half of it, and it shows up in the urine as creatinine.

These cases illustrate the vital importance of properly interpreting lab-test results. Yet many bodybuilders—and others—don’t bother to have such essential tests done, or do so rarely. That’s a major mistake, since the tests can alert you to future health problems. Much of the damage done by cardiovascular disease, for example, is symptom-free. You feel nothing until a major event, such as a heart attack or stroke, occurs—often the culmination of long-term, silent damage that could have been avoided with preemptive medical treatment.

Although so-called sex hormones, such as testosterone and estrogen, aren’t measured unless specifically requested, it’s important for bodybuilding progress to know where you are with them. That’s particularly true of men, whose testosterone levels tend to drop after age 40. Since testosterone is absolutely vital to building muscle, having low testosterone will either hamper muscular gains or make them unlikely. Men who have elevated estrogen levels can experience symptoms that include decreased libido, or sex drive, and gynecomastia, or male breasts.

In the first part of this series on laboratory blood testing, we’ll examine and interpret tests for testosterone, estrogen, luteinizing hormone, follicle-stimulating hormone and dihydrotestosterone.

 Total and Free Testosterone

 If you want a good picture of how the testosterone blood test works, it helps to know something about laboratory protocols and testosterone metabolism in the body. What the testing industry calls reference lab values for total testosterone vary among labs but are usually in the neighborhood of 300 to 1,000 nanograms per deciliter of blood. A nanogram is a billionth of a gram.

Testosterone is synthesized in the male body from the starting substance of cholesterol, which is transported to the testes by way of low-density lipoprotein (LDL) in the blood. The synthesis of testosterone, however, begins in the brain with the release of gonadotropin-releasing hormone (GRH) from the hypothalamus. GRH then travels in the body’s portal system, a kind of special vascular expressway, to the pituitary gland. There, luteinizing hormone, or LH, is released. LH then travels to the Leydig cells of the testes, where it dictates testosterone synthesis from its cholesterol precursor by stimulating a specific rate-limiting enzyme.

What happens next is an enzymatic cascade that culminates in the synthesis of testosterone. Healthy adult men produce between 2.5 and 11 milligrams of testosterone each day, leading to those normal blood plasma levels of 300 to 1,000 nanograms per deciliter.

An important point is that most of the testosterone circulating in the blood is bound to a protein called sex-hormone-binding globulin, or SHBG, which is synthesized in the liver. About 44 percent of circulating testosterone is bound to this protein, while another 54 percent is bound to albumin, another blood protein. Albumin-attached testosterone can readily be released as needed in the blood capillary beds. The remaining 2 percent of testosterone in the blood is unbound, or free. Only the free testosterone can interact with cellular androgen receptors, making it the only portion of the hormone considered immediately biologically active. What is called total testosterone includes both free and bound forms of the hormone.

In some tissues, such as the prostate gland and seminal vesicles, testosterone is converted by way of an enzyme called 5-alpha reductase into dihydrotestosterone, or DHT. If free, or unbound, testosterone encounters an enzyme called aromatase—found in many parts of the body, including muscle, the brain and especially fat—it’s rapidly converted into estrogen.

Women, whose ovaries and adrenal glands are sites of testosterone production, derive about 50 percent of their testosterone from the conversion of androstenedione, an adrenal androgen, into estrogen from the actions of aromatase in bodyfat. Normal blood testosterone levels in women range from 15 to 65 nanograms per deciliter. Aromatase accounts for much of the testosterone in women that converts into estrogen in their fat tissues.

Doctors will normally order a test for total blood testosterone only if they suspect either hypogonadism or low testosterone output in men or hirsutism (excess hairiness) or diseases characterized by elevated testosterone levels in women. Few doctors ever order a separate test for free testosterone, which at first appears paradoxical, since only its free form is active.

The problem with free-testosterone blood tests is that they’re notoriously inaccurate.1 Drinking alcohol before the test can lead to values artificially lower in men and artificially higher in women. Stress or exhaustion can likewise lead to artificially low testosterone levels. In young men who are sleep-deprived, testosterone levels can drop by as much as 40 percent. When stress hormones such as cortisol are high, testosterone levels drop. Growth hormone raises testosterone levels, and insulin increases free testosterone because it inhibits the synthesis of SHBG in the liver. Thyroid hormone increases SHBG and lowers free testosterone, though total testosterone remains unaffected. Increased estrogen in men lowers both free and total testosterone.

A more reliable way of figuring out the true free-testosterone level is to measure both total test and SHBG, dividing the first value by the second and multiplying by 100, to arrive at a figure known as the free-androgen index. Normal FAI values are between 70 and 100 percent and may fall below 50 percent in older men.

A current controversy in medicine is whether older men deficient in testosterone should take a drug form of the hormone. Some scientists say that just as women’s estrogen levels drop with age, so men’s testosterone levels decline. And just as women experience adverse symptoms from the lower estrogen levels, men deficient in testosterone have symptoms too. They include muscle wasting, depression, loss of cognitive ability and an increased chance of developing Alzheimer’s disease, decreased libido, increased bodyfat (particularly in the belly area) and other complaints.

Giving testosterone to men of any age who are deficient in it results in near miraculous beneficial changes. Zest for life returns, and joints and muscles feel stronger. Spare tires around the waist tend to shrink, especially if the men also diet and exercise properly.

Testosterone is absolutely required for building muscle. The question of whether supplemental versions of it help build muscle was definitively answered in a 1996 landmark study in which subjects were injected with 600 milligrams of testosterone a month. Those who lifted weights showed significantly greater muscle gains than those lifting without the hormone injections.

Some object to using supplemental testosterone under any conditions because of its alleged side effects: increased risk of prostate cancer; prostate enlargement; increased hematocrit, or thickness of blood, a risk factor for strokes; sleep apnea, a temporary cessation of breathing during sleep linked to cardiovascular disease; gynecomastia; and water retention.

Literature on those side effects is scarce, however, and taking testosterone to supplement a deficiency may be as benign as taking vitamins. Controversy continues, but emerging evidence shows that DHT and estrogen may be more involved than testosterone in causing prostate problems. Several experimental forms of testosterone offer its beneficial effects minus most of the side effects, though those newer forms have little or no anabolic effects in muscle.

One such designer androgen involves adding a 7-methyl group to 19-nortestosterone, better known as Durabolin, or nandrolone. This drug isn’t subject to conversion into DHT by way of 5-alpha reductase enzyme but retains much of the androgenic benefits associated with regular testosterone. The main advantage is less prostate-gland stimulation than testosterone gives you. The newer drugs will be available in either implant or dermal-release forms, thus preventing superphysiological levels of testosterone. They would maintain existing muscle mass but not promote any pronounced anabolic effect, which would require far higher levels of testosterone.

It’s best to test for blood testosterone levels in the early-morning, no later than 8 a.m., since that’s when the hormone normally peaks in men.

 Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH)

LH and FSH tests are generally used to determine the cause of infertility, especially in women. They may also be ordered for men who have gynecomastia. If LH is low, testosterone synthesis is also low, and that can occur even when normal testosterone-secreting cells are working properly. In males normal LH levels are 1.24 to 7.8 and FSH levels are 1.42 to 15.4. In women the values of both hormones fluctuate, depending on where they are in their monthly cycles. In addition, both hormones have a pulsatile secretion, meaning they’re released intermittently every 20 minutes or so. That mandates either several measurements or several urinary tests at 24-hour intervals.

FSH and LH are measured in men primarily to see if low testosterone or sperm levels imply testes or pituitary-gland defects. LH levels normally rise with age, theoretically because the Leydig cells have trouble interacting with the hormone, which lowers testosterone. The body responds by attempting to upregulate testosterone synthesis by secreting more LH and FSH.

In women these gonadotropins, as they’re called, also increase with age as estrogen production declines. Elevated LH and FSH levels in older women are linked to hot flashes, or vasomotor instability, the name given to the sudden dilation of blood vessels that leads to a feeling of intense body heat.

Some forms of anabolic steroids shut down the body’s testosterone synthesis. Many bodybuilders attempt to compensate by injecting HCG (Pregnyl), normally made in a woman’s body shortly after pregnancy. HCG is nearly identical to LH and to a certain extent does increase testosterone synthesis. But it also increases estrogen synthesis, leading to the usual side effects.

 Dihydrotestosterone (DHT)

 A by-product of testosterone metabolism, DHT is produced by actions of the enzyme 5-alpha reductase on testosterone in the blood. DHT binds to some tissues, such as prostate-gland tissue, more tightly than even testosterone itself. The body needs DHT for the formation of male structures, such as the genitals, pubic hair, beard growth and so on. Males born lacking the 5-alpha reductase enzyme are often raised as girls, since they have “ambiguous” genitalia.

DHT is also often called “testosterone’s evil twin” because of its involvement in male-pattern baldness, acne and prostate enlargement, but some DHT may be important for building muscle and maintaining normal sex drive. DHT tests are usually used only for cases of male pseudohermaphroditism, testosterone-production-enzyme deficiency, congenital adrenal hyperplasia and certain adrenal-gland tumors. A popular medication that partially inhibits 5-alpha reductase activity and thus lowers DHT is finasteride, which is sold under the trade names Proscar and Propecia. The former is used to treat prostate-gland enlargement, the latter, at one-fifth the dosage for prostate problems, to treat male-pattern baldness.

 Estrogen

 Normal estrogen levels in men range from 10 to 50 picograms per milliliter of blood. Estrogen levels in women vary with the status of their menstrual cycle, and most of it is produced in the ovaries. Estrogen takes three forms, estradiol being the most active by far. In women, measuring estrogen evaluates ovarian function.

In men, measuring estrogen can reveal an imbalance between testosterone and estrogen. Anabolic-steroid users can also profit from knowing their estrogen levels, since many steroid drugs are converted into estrogen by way of aromatase. Drugs for blocking that enzyme include Arimedix. Estrogen does have some beneficial effects in men—it’s required for the normal maturation and synthesis of sperm cells—so cutting it out totally can lead to problems.

 Reference

1 Rosner, W. (2001). An extraordinarily inaccurate assay for free testosterone is still with us. J Clin Endocrin Metab. 86:2903.

©,2013 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited.


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The Applied Ergogenics blog is a collection of articles written and published by Jerry Brainum over the past 20 years. These articles have appeared in Muscle and Fitness, Ironman, and other magazines. Many of the posts on the blog are original articles, having appeared here for the first time. For Jerry’s most recent articles, which are far more in depth than anything that appears on this blog site, please subscribe to his Applied Metabolics Newsletter, at www.appliedmetabolics.com. This newsletter, which is more correctly referred to as a monthly e-book, since its average length is 35 to 40 pages, contains the latest findings about nutrition, exercise science, fat-loss, anti-aging, ergogenic aids, food supplements, and other topics. For 33 cents a day you get the benefit of Jerry’s 53 years of writing and intense study of all matters pertaining to fitness,health, bodybuilding, and disease prevention.

 

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